Diarylmethylamines are an important class of amines present in many compounds with biological activity, for example diarylmethylpiperazines, and constitutes key intermediates in the synthesis of these compounds. Most preparations of enantiomerically pure diarylmethyl-amines and -piperazines rely on resolution of diastereomers by crystallization were half of the material is discarded.
There are few reports on asymmetric synthesis of diarylmethylpiperazines. The present invention describes a simple and practical process for asymmetric synthesis of diarylmethylpiperazines in high yield and enantiomeric purity with asymmetric diarylmethylamines as intermediates. The process relies on diastereoselective addition of organometallic compounds to chiral sulfinimines.
Diarylmethylpiperazines derivatives are known from inter alia WO 93/15062, WO 95/04051, and WO 97/23466 to have analgesic effect. The diarylmethylpiperazines derivatives are prepared starting from an N-unsubstituted piperazine derivative which is thereafter alkylated to give the desired diarylmethylpiperazines.